Oral health topics: antibiotic prophylaxis prior to dental procedures. American Dental Association website.
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OTC Case Studies: Cardiovascular Disease Conundrum
Through the combination of dietary changes including daily consumption of plant sterol or plant stanol and increased physical activity this patient successfully lost weight and improved his cardiovascular risk profile. The abnormal relaxation pattern of the left ventricle disappeared and the physical performance capacity of the patient significantly improved. Blood pressure was well controlled on treatment with Ramipril 10 mg daily. Vitamin D remains subnormal. LDL cholesterol decreased by 39 percent and is within the recommended target range, HDL cholesterol increased by 21 percent, triglycerides slightly improved.
Drugs for lowering cholesterol have not been required.
Infection, Immunity & Cardiovascular Disease
The patient was encouraged to maintain the diet and lifestyle changes to continue to manage LDL cholesterol. The patient was also advised to continue Ramipril 10mg daily for continued control of blood pressure. What are the cardiovascular benefits of including plant sterols and stanols in a healthy lifestyle? Given that people with diabetes were excluded from this trial, it does not inform decision-making for Roberta. An additional recommendation is to have lower systolic targets — such as mmHg for younger patients, those with albuminuria, and patients with additional cardiovascular disease risk factors if the patient can tolerate additional treatment.
To that end, adding hydrochlorothiazide in combination with the lisinopril to try to get Roberta's blood pressure closer to mmHg makes sense. The role of aspirin is evolving in the prevention of cardiovascular events. For patients such as Roberta, adding a daily aspirin at 81 mg is advisable given that the benefits in CVD risk reduction far outweigh the bleeding risk in her situation.
To diagnose the "why," the clinician should first and foremost assess Roberta's adherence to metformin. Given the high rate of non-adherence to medications for chronic disease, it would be pointless to further intensify treatment if she has simply stopped taking it!
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It would also be valuable to ask Roberta how important it is for her to get better control of her blood sugar. If her answers suggest that she is not convinced of the importance of good glycemic control, she should be reeducated with data showing improved outcomes for microvascular complications of diabetes associated with good glycemic control. Once it is established that better glucose control is essential and that Roberta is adherent to her metformin regimen, new options can be reviewed as well.
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For the first time, medications are available that can help Roberta control her glucose but that also have the potential to reduce her risk of having another heart attack. Despite past concerns that intensive antihyperglycemic therapies might jeopardize cardiovascular safety, Roberta can be assured that glycemic control and improved cardiovascular outcomes can now go hand-in-hand. In fact, recent evidence has associated certain newer antihyperglycemic medications with reductions in macrovascular, not just microvascular, complications of type 2 diabetes. Just what should the add-on medication be?
Almost certainly not a sulfonylurea drug, given the associated weight gain seen with the class already a concern of Roberta's and the propensity to cause hypoglycemia.
There are also questions about how effective a sulfonylurea drug would be over the long term relative to other agents. Adding basal insulin at this point would lead to additional weight gain. Changing the metformin and replacing it with basal insulin at this point would similarly lead to additional weight gain. On the other hand, to squeeze perhaps more glycemic control and potential weight loss out of a drug that she is already tolerating, her clinician might consider an increase in metformin to 2, mg per day and assess tolerability.
Should nausea or other GI side effects develop at 2, mg, dosage should be backed down to the 1 gram per day. There are no demonstrable benefits in increasing metformin beyond 2, mg per day, only an increased risk of GI side effects. In fact, while Roberta is already in advanced cardiovascular disease, this more aggressive approach can make sense even for patients earlier in their disease course.
The combination of all three agents SGLT2 inhibitor, GLP-1 analog, and metformin is an evolving paradigm of care given the synergies of effectiveness, low rates of hypoglycemia, and weight loss. Yet another option might be to add a DPP-4 inhibitor, particularly if Roberta refuses an injectable and has an SGLT2 contraindication such as recurrent urinary tract infections UTIs or mycotic vaginal infections— especially as there are now several metformin combination options. Unlike the sulfonylureas, this highly used class of oral agents has the benefit of being weight-neutral — with the potential for some weight loss.
Its low associated risk of hypoglycemia, especially when used with metformin, is another benefit. Associated with weight loss, SGLT2s can be given as either monotherapy or add-on therapies and, like the DPP-4 agents, can be provided in a fixed-dose combination.